Myeloma kidney, a cast nephropathy, is a common cause of death in patients with myeloma. It is postulated that a primary factor in the pathogenesis of this condition is polymerization and precipitation of filtered light chain in the tubular lumen. Recent in vitro experiments have shown that urinary light chains may form fibrillar, polymer precipitates on incubation with pepsin or kidney lysosomal extract at acid pH. It is planned here to study the in vivo handling of light chains under conditions which may enhance luminal protein precipitation. Using purified and characterized light chains from a few well-studied patients with Bence Jones proteinuria and renal disease, a rat model we have previously described for studying renal handling of light chain will be modified by the following factors alone and in combination: (1) Hydropenia; (2) Acid loading; (3) Lysosmal enzymuria produced by injection of D serine or prior injection of light chains. In vitro incubation of the various light chains will be performed with pepsin, rat kiney extract, normal rat urine, and urine from rats with tubular damage. Renal tissue will be studied by light and electronmicroscopy and by thin section freeze substitution immunohistology, and changes assessed by blind semiquantitative scoring. It is hoped in this way to set up an animal model for myeloma kiney and to delineate the factors important in its pathogenesis.